The long-term objective of this project is to bring to clinical practice a novel technology for the real-time and non-invasive measurement of cancer-related analytes. This technology consists of a sensor implanted at the time of a tumor biopsy to allow subsequent monitoring of tumor analytes such as pH and p02 through magnetic resonance methods. The specific aims of the project are as follows: design and execute preclinical studies in support of a Premarl<et Approval Application to the FDA, and develop a new approach to construction of the sensors. Sensors will first be validated in a mouse model designed to show differential response to chemotherapy for the pH sensor, and temporal response to irradiation in the case of the p02 sensor. These models will allow the correlation of sensor measurements to therapeutic efficacy in mice and provide in vivo validation of the devices. A preclinical study in dogs with endogenous tumors will then follow to test the devices in actual canine subjects, a particularly important step given that canine tumor models exhibit biological behavior similar to human cancers. Results from these studies will provide supporting evidence for a Premarket Approval Application to the FDA. The second aim in this project is the development of two minimally-invasive sensor formats with reduced dimensions compared to the current sensor size. Each of these formats will afford a different advantage to the device. The biopsy-implantable sensor, fitted with a coil, will allow reading of the device without the use of a costly MRI scanner, while the injectable sensor will simplify the implantation procedure ofthe device, without requiring surgery or a biopsy. The biopsy-implantable sensor will be validated in vitro and in vivo by pH measurements with a benchtop one-sided NMR, using the mouse model developed forthe first specific aim. The injectable sensor will consist of 3 parts which may be investigated concurrently: fabrication of semi-permeable microspheres containing the sensing agent; development ofthe injectable device matrix; and in situ control ofthe size and shape of the device. The device will be validated in vitro and in vivo similarly to the biopsy-implantable sensor.